Induced Skin Damage Research Articles

Ergothioneine alleviates senescence of fibroblasts induced by UVB damage of keratinocytes via activation of the Nrf2/HO-1 pathway and HSP70 in keratinocytes

Ultraviolet B (UVB) irradiation induces skin damage and photoaging through several deleterious effects, including generation of reactive oxygen species (ROS), apoptosis of epidermal cells, inflammation, and collagen degradation in fibroblasts. Ergothioneine (EGT) is a naturally occurring amino acid with potential biological properties. We evaluated whether EGT protects against UVB-induced photoaging using a keratinocyte/fibroblast co-culture system. Keratinocytes were pretreated with EGT, irradiated with UVB, and co-cultured with fibroblasts. In keratinocytes, ROS production and apoptosis were assessed. We also analyzed the Nrf2/HO-1 pathway, HSP70, proapoptotic proteins, and paracrine cytokines by Western blotting and real-time PCR. Collagen degradation-related genes and senescence were also assessed in fibroblasts. EGT pretreatment of keratinocytes significantly inhibited downregulation of the Nrf2/HO-1 pathway and HSP70, and protected keratinocytes by suppressing production of ROS and cleavage of proapoptotic proteins, including caspase-8 and PARP. Furthermore, EGT significantly reduced the paracrine cytokines, including IL-1β, IL-6, and TNF-α. In co-cultures of fibroblasts with EGT-treated keratinocytes, the expression levels of collagen degradation-related genes and fibroblast senescence were significantly decreased; however, synthesis of procollagen type I was significantly increased. Our results confirm that EGT suppresses the modification of collagen homeostasis in fibroblasts by preventing downregulation of the Nrf2/HO-1 pathway and HSP70 in keratinocytes following UVB irradiation.

Geniposide, a Principal Component of Gardeniae Fructus, Protects Skin from Diesel Exhaust Particulate Matter-Induced Oxidative Damage

Gardeniae Fructus (GF) is the fruit of Gardenia jasminoides Ellis and is traditionally prescribed to treat pyogenic infections and skin ulcers. This study investigated the protective effects of GF and the underlying mechanism responsible for these effects on diesel exhaust particulate matter- (DEP-) induced skin damage. The protective effects of an ethanolic extract of GF (GFE) and its constituents (geniposidic acid, gardenoside, geniposide, chlorogenic acid, and genipin) were examined by analyzing reactive oxygen species (ROS) production, apoptosis, and tight junction (TJ) protein expression in HaCaT cells. Treatment with GFE dose-dependently inhibited intracellular ROS production and apoptosis by regulating the protein expressions of Bax, Bcl-2, and cytochrome C in DEP-stimulated (100 μg/ml) HaCaT cells. Mechanistic studies revealed that the protective effects of GFE were related to its activation of Nrf2 and HO-1 signaling in HaCaT cells. Geniposide, a main constituent of GFE, enhanced the expression of occludin in DEP-stimulated HaCaT cells. Furthermore, topical application of geniposide reduced the expressions of 8-OHdG and Bax and increased the expression of occludin in the dorsal skin lesions of DEP-stimulated mice. Gardeniae Fructus and its main component geniposide are potential candidates for the repair of DEP-induced skin damage due to their antioxidant and antiapoptotic activities.

Glabridin Liposome Ameliorating UVB-Induced Erythema and Lethery Skin by Suppressing Inflammatory Cytokine Production.

Glabridin, a compound of the flavonoid, has shown outstanding skin-whitening and anti-aging properties, but its water insolubility limits its wide application. Therefore, glabridin liposome (GL) has been developed to improve its poor bioavailability, while there are few studies to evaluate its amelioration of UVB- induced photoaging. This study is performed to investigate the amelioration of GL against UVB- induced cutaneous photoaging. The prepared GL has a spheroidal morphology with an average diameter of 200 nm. The GL shows lower cytotoxicity than glabridin, but it has a more effective role in inhibition of melanin. Moreover, the application of GL can effectively relieve UV radiation induced erythema and leathery skin, associated with the down-regulated expression of inflammatory cytokines (TNF-α, IL-6 and IL-10). Taken together, these results demonstrate that GL has potentials as topical therapeutic agents against UVB radiation induced skin damage through inhibiting inflammation.

Effect of UV irradiation on surface of collagen film

It is well known that ultraviolet (UV) radiation is considered to be one of the most hazardous external factor that induces skin damage, leading in some cases to skin carcinoma. The most abundant protein in human skin tissue is collagen, which is responsible for conferring strength and resiliency. Taking into account these aspects, the present paper study the influence of the UV-irradiation on surface of a collagen film. Thus, the surface modification of the collagen film after irradiation was monitored with the help of the FTIR spectroscopy in close correlation with contact angle determinations and profilometry analysis. The obtained data reveal that after UV-irradiation, the collagen film has shown different structural changes which depend on the irradiation time. At short irradiation time, some cleavage and reorganization of the surface structural groups take place, but in contrast, the highest radiation exposure led to degradation.

Chemical Composition of a Novel Distillate from Fermented Mixture of Nine Anti-Inflammatory Herbs and Its UVB-Protective Efficacy in Mouse Dorsal Skin via Attenuating Collagen Disruption and Inflammation.

Since ancient times, various herbs have been used in Asia, including Korea, China, and Japan, for wound healing and antiaging of the skin. In this study, we manufactured and chemically analyzed a novel distillate obtained from a fermented mixture of nine anti-inflammatory herbs (Angelica gigas, Lonicera japonica, Dictamnus dasycarpus Turcz., D. opposita Thunb., Ulmus davidiana var. japonica, Hordeum vulgare var. hexastichon Aschers., Xanthium strumarium L., Cnidium officinale, and Houttuynia cordata Thunb.). The fermentation of natural plants possesses beneficial effects in living systems. These activities are attributed to the chemical conversion of the parent plants to functional constituents which show more potent biological activities. In our current study, the distillate has been manufactured after fermenting the nine oriental medical plants with Lactobacillus fermentum, followed by distilling. We analyzed the chemical ingredients involved in the distillate and evaluated the effects of topical application of the distillate on ultraviolet B (UVB)-induced skin damage in Institute of Cancer Research (ICR) mice. Topical application of the distillate significantly ameliorated the macroscopic and microscopic morphology of the dorsal skin against photodamage induced by UVB radiation. Additionally, our current results showed that topical application of the distillate alleviated collagen disruption and reduced levels of proinflammatory cytokines (tumor necrosis factor alpha and interleukin 1 β expressions) in the dorsal skin against UVB radiation. Taken together, our current findings suggest that the distillate has a potential to be used as a material to develop a photoprotective adjuvant.

Pegylated catalase as a potential alternative to treat vitiligo and UV induced skin damage

The metabolic function of catalase (CAT) is to prevent oxidative damage to tissues through the hydrolysis of hydrogen peroxide, which is a strong oxidizing agent. It has been suggested as an alternative to treat skin diseases related to oxidative stress, such as vitiligo. Owing to the instability associated to the protein nature, topical use of CAT is challenging and, in this sense, PEGylation can be an interesting alternative. Here, we conjugated CAT to methoxy-poly(ethylene oxide) (mPEG) of 10, 20 and 40 kDa, by means of a nucleophilic attack of ε-amino groups to an electron-deficient carbonyl group of the reactive PEG, resulting in site specifically PEGylated bioconjugates. PEGylation yields ranged from 31% ± 2% for CAT-PEG40 to 59% ± 4% for CAT-PEG20 and were strongly affected by the reaction pH owing to the protonation/deprotonation state of primary amines of lysine and N-terminal residues. PEGylated conjugates were purified by size-exclusion chromatography (purity > 95%) and characterized by circular dichroism. Irrespectively of MW, PEG did not affected CAT secondary and tertiary structure, but a decrease in specific activity was observed, more pronounced when PEGs of higher MWs were used. However, this loss of activity is compensated by the increased long-term stability, with a gain of >5 times in t1/2. In vitro antioxidant activity of CAT-PEG20 showed complete elimination of lipid peroxidation at the skin upper layer (stratum corneum) suitable for a topical use to treat vitiligo, as well as other skin conditions related to oxidative stress.

Evaluating the effect of ozone in UV induced skin damage

Air pollution represents one of the main risks for both environment and human health. The rapid urbanization has been leading to a continuous release of harmful manmade substances into the atmosphere which are associated to the exacerbation of several pathologies. The skin is the main barrier of our body against the external environment and it is the main target for the outdoor stressors. Among the pollutants, Ozone (O3) is one of the most toxic, able to initiate oxidative reactions and activate inflammatory response, leading to the onset of several skin conditions. Moreover, skin is daily subjected to the activity of Ultraviolet Radiation which are well known to induce harmful cutaneous effects including skin aging and sunburn. Even though both UV and O3 are able to affect the skin homeostasis, very few studies have investigated their possible additive effect. Therefore, in this study we evaluated the effect of the combined exposure of O3 and UV in inducing skin damage, by exposing human skin explants to UV alone or in combination with O3 for 4-days. Markers related to inflammation, redox homeostasis and tissue structure were analyzed. Our results demonstrated that O3 is able to amplify the UV induced skin oxinflammation markers.

16030 Topical application of vitamin C and E compound mixture prevents combined pollutant-induced skin inflammation, oxidation, and loss of cutaneous barrier proteins

The skin is one of the main target organs of the harmful effects of environmental insults. In fact, ozone (O3), particulate matter (PM), and ultraviolet (UV) light have all been shown to induce skin damage through disruption of redox homeostasis and induction of pro-inflammatory status, resulting in an OxInflammation feedback. In the past few decades, several studies have been focused on the effect of pollution on cutaneous tissues, although very few have investigated the additive effects of different pollutants.

17999 Evaluation of ascorbic acid and a capsulated ascorbic acid-containing serum for protection against ambient particulate matter

Background: Air pollution causes severe damage to the skin but is less recognized in this context than UV radiation. It has been shown that particulate matter with a diameter less than 2.5 micrometers (PM2.5), a major component of air pollution, induces skin damage partially through overproduction of reactive oxygen species (ROS). Ascorbic acid (vitamin C) is a known antioxidant that may protect the skin from pollution and UV. However, ascorbic acid is easily degraded during storage. This study aimed to evaluate the efficacy of ascorbic acid and its more stable derivatives, as well as a capsulated ascorbic acid–containing serum, against PM2.5- and UV-induced ROS overproduction.

Ethanol consumption synergistically increases ultraviolet radiation induced skin damage and immune dysfunction

BackgroundExcessive UV radiation disrupts skin homeostasis by multiple mechanisms that extend beyond the simple erythema associated with sunburns including reduction of antioxidants, increased DNA damage, and impairment of skin immune responses. Recreational UV exposure frequently occurs concurrently with excessive ethanol (EtOH). Epidemiological studies suggest a harmful, dose-dependent impact of EtOH in the setting of high UV exposure, leading to increased severity of sunburns relative to those generated in the absence of EtOH. Furthermore, EtOH consumption and UV radiation have multiple overlapping effects on the skin that could account for the epidemiological association. ObjectiveTo elucidate the relationship between excessive EtOH ingestion and UV exposures on early skin damage and downstream immune dysfunction. MethodsWe examined the impact of UVB on local skin damage, including inflammation, sunburned cells, apoptotic cells, melanin and antioxidant levels, DNA damage and immune dysfunction in the presence or absence of EtOH ingestion by combining standard mouse models of EtOH consumption and UVB exposure models. To confirm that the observed changes in mouse skin were relevant to human skin, we investigated the effects of EtOH on UV-induced skin damage with human skin explants. ResultsWe demonstrated that EtOH consumption and UV exposure act synergistically to increase the severity of local skin damage resulting in impaired melanin responses, reduced antioxidants, greater DNA damage, and immune dysfunction as measured by reduced contact hypersensitivity. ConclusionsThe results support incorporation of the risks of combined UV exposure and excessive alcohol consumption into public health campaigns.

Evaluation of the Antioxidant Properties of Vitellaria paradoxa Seed Extract and Its Effect of Ultra Violet Radiation Induced Skin Damage

Ultra violet radiation (UVR) is relevant in nature, but despite its importance it has been labeled as a causative agent in skin damage. This study was done to evaluate the antioxidant properties of shea butter and its role in the prevention of skin damage. Six groups of albino rats with three rats per group were used, group 2-5 were exposed to UVR at the dose of 180 mJ/cm2 with group 1 serving as the normal control, group 2 (negative control), group 2-5 (treated groups) and group 6 (normal + treated). The treatment was done by topical application of Vitellaria parodoxa seed extract 5 minutes after exposure to UVR. The in-vitro antioxidant properties determined using DPPH radical scavenging activity revealed that the aqueous extract of Vitellaria paradoxa possesses high antioxidant activity. There was an increase in the concentration of GSH of the treated animals when compared to the negative control (p<0.05). The histopathology result shows the extract had a protective effect on the skin tissue of the experimental animals. This study suggests the extract has the potential to serve as a chemopreventive agent against UV-induced skin damage by neutralizing the effects of free radicals generated by ultraviolet radiation and as such can be recommended for use as UVR screen which could in turn reduce the risk of UVR skin damage.

Metformin effect on driving cell survival pathway through inhibition of UVB-induced ROS formation in human keratinocytes

Human skin functions go beyond serving only as a mechanical barrier. As a complex organ, the skin is capable to cope with external stressors cutaneous by neuroendocrine systems to control homeostasis. However, constant skin exposure to ultraviolet (UV) radiation causes progressive damage to cellular skin constituents, mainly due excessive reactive oxygen species (ROS) production. The present study shows new approaches of metformin (MET) as an antioxidant agent. Currently, MET is the first line treatment of type 2 diabetes and has attracted attention, based on its broad mechanism of action. Therefore, we evaluated MET antioxidant potential in cell-free systems and in UVB irradiated human keratinocyte HaCaT cells. In cell-free system assays MET did not show intrinsic scavenging activity on DPPH radicals or superoxide (O2−) xanthine/luminol/xanthine oxidase-generated. Cell-based results demonstrated that MET was able to reduce UVB-induced intracellular ROS and NADPH oxidase-dependent superoxide (O2−) production. MET posttreatment of HaCaT cells reduced ERK 1/2 phosphorylation, NADPH oxidase activity, and cell death by apoptosis. These findings suggest that the protection mechanism of MET may be through the inhibition of ROS formation enzyme. These results showed that MET might be a promising antioxidant agent against UV radiation induced skin damage.

Macroalgae Sargassum cristaefolium Extract Inhibits Proinflammatory Cytokine Expression in BALB/C Mice.

Ultraviolet radiation (UVR) which could induce skin damage and skin disease is a growing concern due to the increase in global warming. Brown macroalgae Sargassum cristaefolium has been recognized to exhibit UV protective activities. However, the mechanism of its photoprotective activity remains unclear. The purpose of this study is to investigate the potential mechanism of S. cristaefolium's photoprotective activity against UV radiation. Phytochemical analyses revealed valuable bioactive compounds in SCE, such as fucoxanthin which is widely known as an anti-inflammatory carotenoid. Treatment with SCE before UV-A radiation show reduced levels of wrinkles and desquamation. Interestingly, SCE treatment induces the skin healing process after UV radiation. SCE effectively inhibited proinflammatory TNF-α and IL-6 expression while increasing IL-10 production in the BALB/c mice skin. Current results suggest that SCE potentially protects the skin by attenuation of inflammatory cytokines. In addition, SCE demonstrates promising antibacterial activity (MIC = 1.302 µg/mL) against Staphylococcus aureus. Overall, SCE could be a source of an effective anti-inflammatory agent protecting against UV irradiation-induced skin damages.

Persimmon oligomeric proanthocyanidins alleviate ultraviolet B-induced skin damage by regulating oxidative stress and inflammatory responses

Skin damage can be induced by excessive ultraviolet B (UV-B) irradiation. This study aimed to investigate the potential protective activity of persimmon oligo-proanthocyanidins (P-OPC) against UV-B induced human keratinocyte cells (HaCaT cells) and skin damage and its underlying mechanisms in vitro and in vivo. P-OPC was shown to inhibit the production of intracellular reactive oxygen species (ROS) induced by UVB radiation in both HaCaT cells and mouse skin tissues by increasing the activity of the antioxidant enzyme system [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH)]. Furthermore, P-OPC was found to suppress cell apoptosis and the production of inflammatory cytokines, TNF-α, and IL-6. Overall, P-OPC could protect skin tissues from UV-B-induced damage by suppressing oxidant stress, acute inflammation, and cell apoptosis via regulating MAPK and NF-κB signalling pathways. These results indicate the potential of P-OPC as a photochemo-protective agent against UV-B induced skin damage.

English

Anacardium occidentale nut shell liquid has been used for decades especially by natives of South America, Asia and Africa in the treatment of topical skin diseases, abrasion and cancerous ulcers amongst others. Chronic exposure to sunlight can lead to skin damages including erythema, edema, hyperplasia, formation of sunburn cells, photo-aging, suppression of the immune system and skin cancer. This study was aimed at evaluating the effect of methanol extract of A. occidentale nut shell liquid on UV radiation (UVR) induced skin damage and cancer initiation. Gas chromatography and mass spectroscopic (GC-MS) analysis was carried out on the extract. Skin damage was induced by exposing the hairless part of the experimental animals directly to UVR (180 mJ/cm2 daily) for 42 days alongside treatment with the extract. Percentage weight gain, relative organ weight, lipid peroxidation and histological studies were carried out. The methanol extract of CNS as determined by GC-MS analysis contains 1,2,3-Benzenetriol and benzofuran. A normal skin tissue and hepatocyte was observed in the normal control, severe wrinkling of skin epithelium with actinic keratosis of the dermal collagen and marked venous congestion in the liver of the negative control and complete recovery in the group treated with 300 mg/kg of the extract was observed. This study suggests that the administration of the extract exhibited a chemopreventive effect against skin damage which could lead to cancer initiation stage resulting from ultraviolet radiation by preventing its detrimental impact on the epidermis. Key words: Anacardium occidentale (Cashew), chemo-preventive effect, bioactive compounds, skin damage, ultra-violet radiation.

Effects of adenosine triphosphate on vandetanib induced skin damage in rats

Purpose Vandetanib is a wide spectrum tyrosine kinase inhibitor used for the treatment of metastatic medullary thyroid cancer (MTC) and various other cancer types. Although it is usually well-tolerated ıt has been linked to a variety of severe dermatologic reactions. Our study aimed was to investigate adenosine 5′-triphosphate (ATP) on vandetanib-induced skin damage. Materials and methods A total number of 18 rats were divided into three equal groups as vandetanib group (VDB), vandetanib plus ATP group (VAT), and healthy group (HG); 25 mg/kg ATP was injected intraperitoneally (ip) to the VAT group. Normal saline was given to the HG and VDB groups as solvent via intraperitoneally. One hour later, 25 mg/kg vandetanib was applied orally via an orogastric catheter in the VAT and VDB groups. This procedure was repeated once daily for 4 weeks. After that period, all animals were sacrificed and their skin tissues removed. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), total antioxidant status (TAS) levels in rats’ skin tissues were evaluated with histopathological analyses. Results MDA and TOS levels measured higher in the VDB group compared to the VAT and HG groups (p < 0.001). tGSH and TAS levels of the VDB group measured lower than the VAT and HG groups (p < 0.001). The structure and morphology of skin tissue were normal in the control group. In the VDB group, skin tissue damage with thinner epitelium, ruptured and degenerated hair follicles, abnormal accumulation of abnormal keratin on the epithelium and oedematous areas in the dermis was observed. In the VAT group, these findings were significantly improved. Conclusion We demonstrated that adenosine triphosphate can prevent vandetanib-induced skin toxicity in rats for the first time. The promising results denote that further studies testing this agent in other animal models and in humans are warranted.

Chemopreventive Effect of Methanol Extract of Anacardium Occidentale Nut Shell on Ultra-Violet Radiation Induced Skin Damage

Anacardium occidentale nut shell liquid which is mostly known as cashew nut shell liquid has been used for decades especially by natives of South America, Asia and Africa in the treatment of topical skin diseases, skin abrasion and cancerous ulcers amongst others. Some previous studies attempted to link pharmacological activities to the antibacterial, antioxidant and anti-proliferative properties of CNSL. Chronic exposure to sunlight can lead to skin damages including erythema, edema, hyperplasia, formation of sunburn cells, photoaging, suppression of the immune system and skin cancer. This study was aimed at evaluating the effect of methanol extract of Anacardium occidentale nut shell liquid on UV induced skin damage and cancer initiation. Gas chromatography and mass spectroscopic analysis was carried out on the extract. Skin damage was induced by exposing the hairless part of the experimental animals (albino rats) directly to UVR for 42 days alongside treatment with methanol extract of cashew nut shell following the experimental design. Percentage weight gain, relative organ weight, lipid peroxidation and histological studies were carried out to evaluate the impact of the UVR exposure and the chemo preventive effect of the extract. The methanol extract of CNS as determined by GC-MS analysis contains 1,2,3-Benzenetriol and benzofuran. A normal skin tissue and hepatocyte was observed in the normal control, severe wrinkling of skin epithelium with actinic keratosis of the dermal collagen and marked venous congestion in the liver of the negative control and complete recovery in the group treated with 300 mg/kg of the extract was observed. Marked serboheic keratosis and venous congestion in the liver was seen in the untreated groups. This study suggest that the administration of methanol extract of CNS exhibited a chemo preventive effect against skin damage which could lead to cancer initiation stage resulting from ultraviolet radiation by preventing its detrimental impact on the epidermis which could in turn lead to DNA damage and subsequently skin cancer initiation. 1,2,3-Benzenetriol and benzofuran which according to previous studies, exhibits anticancer, antioxidant and antibacterial activity were present in the extract, these compounds amongst others are believed to be responsible for the pharmacological activities observed in the study.

350 Histone demethylase LSD1 is required for LC embryonic development but dispensable for LC maintenance and repopulation

Langerhans cells (LCs), the sole dendritic cell subpopulation in the epidermis, are potent regulators of immune surveillance and tolerance. Unlike conventional DCs, LCs follow unique patterns of development and maintenance under steady and inflamed states. Lysine-specific demethylase 1 (LSD1), known to mediate the demethylation of lysine amino acids on histone proteins, plays a key role in the maintenance and differentiation of hematopoietic stem cells. However, the role of LSD1 in LC ontogeny and homeostasis remains unknown. To address this, we generated Csf1rCreLSD1fl/fl conditional knockout (Csf1r.LSD1-KO) mice in which LSD1 was deficient in macrophage/monocytes and LC precursors from embryonic stage. We found a robust reduction of LC precursors in Csf1r.LSD1-KO mice at embryonic day 18.5 and postnatal day 0, suggesting that LSD1 is required for LC ontogeny at late embryonic stage. To investigate whether LSD1 is involved in LC maintenance and repopulation, we created CD11cCreLSD1fl/fl conditional knockout (CD11c.LSD1-KO) mice in which LSD1 was deficient in all DC populations including epidermal LCs after birth. Flow cytometry and immunofluorescent staining of skin showed that the frequency and number of LCs were unaltered in 2-week-old and adult CD11c.LSD1-KO mice compared to wild-type mice. Using an ultraviolet C (UVC)-induced skin damage model, we found that long-term LCs were able to repopulate to the inflamed epidermis of CD11c.LSD1-KO mice 2 weeks after UVC treatment. Overall, our data suggests that LSD1 is critical for LC embryonic development, but not required for the LC maintenance at steady state and repopulation under inflammatory conditions.

Application of laser fluorescence spectroscopy in non-invasive assessment of ultraviolet-induced skin immune response in vivo

Acute ultraviolet (UV) -induced skin damage is associated with structural alterations, vasodilatation and inflammatory response. Leukocyte infiltration is one of the main features of inflammation and could be found in the area of UV injury. It was shown that porphyrins which have well-known autofluorescent properties play a role in the chemoattraction of immune cells to the area of local damage. This study examined the possibility of application of laser fluorescence spectroscopy (LFS) in the assessment of ultraviolet-induced immune response in ICR mice. Animals (N=25) were exposed by UVB light and LFS was conducted on the dorsal skin of each mice 0, 0.5, 3, 6 and 24 hours after UV irradiation. Moreover, in every time point we performed skin biopsy and histology. Using LFS, time-dependent dynamic changes in the fluorescence parameters of porphyrins were found. Mentioned indices were in a good agreement with histological findings. Statistically significant correlation was found between the severity of inflammatory infiltrate and the tissue content index (η) of porphyrins (Pearson correlation coefficient: r = 0.912, p = 0.031). Achieved results not only have fundamental value but could be further investigated and applied in clinical practice: e.g. to objectively predict individual immunologic reaction to UV-light.

Additive effect of combined pollutants to UV induced skin OxInflammation damage. Evaluating the protective topical application of a cosmeceutical mixture formulation

Since the skin is one of the targets of the harmful effects of environmental insults, several studies have investigated the effects of outdoor stressors on cutaneous tissue. Ozone (O3), particulate matter (PM), and ultraviolet radiation (UV) have all been shown to induce skin damage through disruption of tissue redox homeostasis, resulting in the so called “OxInflammation” condition. However, few studies have explored whether these stressors can act synergistically in cutaneous tissues. In the present work, we evaluated whether O3, PM, and UV, which are the most common environmental skin insults, act synergistically in inducing skin damage, and whether this effect could be prevented through topical application of a cosmeceutical formulation mixture (CF Mix) containing 15% vitamin C (l-ascorbic acid), 1% vitamin E (α-tocopherol), and 0.5% ferulic acid. Human skin explants obtained from three different subjects were sequentially exposed to 200 mJ UV light, 0.25 ppm O3 for 2 h, and 30 min of diesel engine exhaust (DEE), alone or in combination for 4 days (time point D1 and D4). We observed a clear additive effect of O3 and DEE in combination with UV in increasing levels of several oxidative (4HNE, HO-1) and inflammatory (COX2, NF-κB) markers and loss of barrier-associated proteins, such as filaggrin and involucrin. Furthermore, daily topical pre-treatment with the CF Mix prevented upregulation of the inflammatory and oxidative markers and the loss of both involucrin and filaggrin. In conclusion, this study is the first to investigate the combined effects of three of the most harmful outdoor stressors on human skin and suggests that daily topical application may prevent pollution-induced skin damage.